Dr. Hector Lopez - Sarcopenia: Exercise, Nutrition and Beyond


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This presentation is originally from 2006, but is still very relevant today. You can contact me with questions here: http://www.drhectorlopez.com/

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  • Myofribrillar proteolysis/ muscle protein turnover.
  • Dr. Hector Lopez - Sarcopenia: Exercise, Nutrition and Beyond

    1. 1. Sarcopenia: Exercise, Nutrition and Beyond Hector Lopez, MD, CSCS, MS(c) Physical Medicine and Rehabilitation RIC-Rehabilitation Institute of Chicago Northwestern University School of Medicine Co-Founder: Physicians Pioneering Performance, LLC Northeast Spine and Sports Medicine, PC.
    2. 2. Outline  Definition/ Epidemiology/ Scope  What’s in a name?  “Players”/ Contributing factors  Intrinsic Muscle cellular/Molecular signaling/  Neuromuscular changes  Cytokine/ Immunologic  Endocrine/ Metabolic (Systemic/ Cell)  Nutritional (Anorexia/Extrinsic and Responsiveness/Intrinsic)  Oxidative Stress  Physical Activity (Bidirectional- Perpetual Cycle)  Atherosclerosis/ PVD  Partial Role of Apoptosis?
    3. 3. Outline (cont.)  Cachexia/Wasting vs. Sarcopenia of Aging  Role of Supplements/Nutritional Strategies  Exercise Strategies  Pharmacologic Adjuncts  On the Horizon
    4. 4. Sarcopenia  Age-related, involuntary loss of muscle mass, strength and function  3-8% loss of muscle mass per decade after 30, steeper after 60  Sarcopenia + Obesity = “fat-frail”  Fundamental cause of disability, functional dependence, falls, worsening outcome from other illness/disease [Baumgartner RN et al. 1999; Morley JE et al. 2001]
    5. 5. Sarcopenia  Prevalence: 35% - 45% of Older US population (>65)  Modifiable public health care cost/ burden – over $60 billion and escalating with senior demographic [Janssen I et al. 2004]  DEXA and RSMI for estimating prevalence [Wang Z et al. 1996; Proctor DN et al. 1999]  Solution to this problem: Multi- disciplinary approach vis a vis Performance Nutrition/ Fitness Professionals
    6. 6. What’s in a name?  Sarcopenia a misnomer?  “Sarco” (G. sarx = flesh)  “Penia” (G. penia = poverty/ deficiency)  “Myo” (G. myos = muscle)  I propose “Myopenia”
    7. 7. “Players” in Sarcopenia  Intrinsic Muscle (Molecular and Cellular)  Reduced muscle cell #, SRetic volume Ca++ handling  Myonuclear centralization, reduced plasma membrane potential/sensitivity, intra-myocellular  Age-related decline in basal/resting MHC, and mixed muscle protein synthesis  Disproportionate atrophy of type IIA muscle fibers  ↓ IGF-1/PI3K/Akt signalling ↑FOXO(forkhead fam TFs), MAFbx/Atrogin (muscle atrogin F-box containing ubiquitin ligase) and MuRF1 (muscle ring finger ub-ligase)  ↓Satellite Cell activation/ signaling for differentiation, recruitment and proliferation (less MHC and CK expression)
    8. 8. “Players” in Sarcopenia  Neuromuscular  Decreased in distal more than proximal MU populations  ↓ # and NCV of α-motor neurons (esp. the larger, faster conducting FF and FFR type)  ↓ Rate firing, Rate coding  ↑ Peripheral sprouting (more distal)  ↓ Neuromusc End-plate area/ folds  Cytokine/ Immunologic  Still many gaps in our knowledge  do know altered cytokine “milieu” w/ aging;  small change in protein catabolism/ anabolism balance X many years = large BComp change
    9. 9. “Players” in Sarcopenia  Cytokine/ Immunologic (cont.)  ↑ tIL-6, IL-1R, systemic TNF, possible relative inc tIL-1 [Roubenoff R et al. 1998]  IL-6 is moderate catabolic cytokine, also functions as regulator of TNF and IL-1R  IL-6 suppresses extensive inflammation in elderly AT the EXPENSE of ….skel muscle proteolysis, AA oxidation/ mobilization  Cytokines confer a “permissive” effect to ‘foster’ sarcopenia with low-grade systemic inflammation as a catabolic backdrop for –’ve muscle protein balance
    10. 10. “Players” in Sarcopenia  Endocrine/Metabolic  Cellular:  ↓Glycogenolytic, Glycolytic capcity, Phosphagen circuit (↓ATP, CrP), TCA cycle enzymes, Mitochondrial Resp Chain Fxn/ mtDNA and mt- protein synth  VO2max decrement  Altered protein metabolism (basal MHC and sarcoplasmic protein synthesis, and mt-Protein synthesis)
    11. 11. “Players” in Sarcopenia  Endocrine/Metabolic  Systemic:  Testosterone- 60% over age of 65 are hypogonadal (Andropause)  ↓DHEA- (Adrenopause)  GH/ IGF-1 axis- gradual decline w/ aging [Lamberts SW et al. 1997]  ↓ Autocrine/ Paracrine MGF/ FGF/ PDGF peptide growth factors  Insulin Resistance at Skeletal Muscle (blunted downstream signaling for protein synthesis in elderly  vast diff in anabolic response to mixed meals young vs. elders) [Rasmussen BB et al. 2006]
    12. 12. “Players” in Sarcopenia  Nutritional/ Intrinsic  Endogenous whole body and muscle protein response to carb-protein (mixed meal feeding) is perturbed: • Insulin appears to abrogate and impair anabolic response of muscle protein to the + effect of AA alone [Dreyer H et al. 2005; Volpi et al. 2000; Rasmussen et al. 2006]  ↓GH pulse magnitude in post- absorptive state
    13. 13. “Players” in Sarcopenia  Nutritional/ Extrinsic  Anorexia of aging: food intake requires complex integration of Periph and Central signals  ↓ fundal relaxation of stomach  ↑ antral stretch of stomach  ↑ CCK release to given fat load  Leptin increases in ♂ throughout lifespan; in ♀ decline in old age  Anorectic cytokines (CilNF, TNF, etc.)  Central regulation-neurotransmitters, endogenous opioids, NPY, endo- cannabinoid/ vanilloid systems  Cross-talk in neurochemistry with Mood
    14. 14. “Players” in Sarcopenia  Oxidative Stress (particularly mt fxn)  ROS/RNS generated in muscle  oxidative stress  Metabolic stressors (Steady state and Exercise), inflammatory stressors, co-existing disease  ~65 yoa- threshold age for imbalance in antioxidant: oxidant: biomolecule homeostasis?  NF-κB activation and inflammatory cascade propagation  ↓nNOS activity  Physical Activity (lack thereof):  Quality and Quantity  Both factor and consequence of Sarcopenia  Bidierctional nature w/ “self-perpetuating” vicious cycle • Feedback and Feedforward Loops
    15. 15. “Players” in Sarcopenia  Atherosclerosis/ PVDz:  Role of microcirculation/ endothelial health in regulating nutrient delivery, anabolic and catabolic stimuli  Role of Apoptosis (individuality)  Cumulative ultra-structural, biochemical damage to SReticulum and mitochondria  Caspase enzyme cascade  Variable depending on co- morbidities/ genotype
    16. 16. Players in Sarcopenia “Chicken or the Egg” Sarcopenia ↓ Physical Activity -Insulin Resistance -Neuromuscular Maladapt. -Cytokine Activity -↓ Type IIa muscle fiber -↓ Anabolic Hormone -↓ Response to Exercise/ Nutritional Stimuli - Oxidative Stress - Anorexia BIDIRECTIONAL
    17. 17. Sarcopenia of Aging VS. Cachexia  Cachexia is a more aggressive, involuntary general weight loss (lean body AND fat mass) occurring SECONDARY to a chronic disease.  Cancer, COPD, HIV/AIDS, CHF, Rheumatoid Arthritis most common for cachexia/wasting
    18. 18. Nutritional Strategies Big Picture Basics:  Maximize whole food nutritional platform  Protein is “King” in the sarcopenic population  Current RDI is 0.8g/Kg/day  Some data on benefit of 1.6g-2.0g/Kg/day  Omega-3 lipids are “Princes” (higher length DHA/EPA)  Immuno-modulation, systemic inflammation, proteasome inhib, eicosanoid milieu, insulin sensitivity, mood/sleep quality, etc. [Calder PC, 2002; Fearon et al. 2003; Smith et al. 2004]
    19. 19. Nutritional Strategies  “CHRONO-Nutrition”  TIMING, TIMING, TIMING! (yes, it works for “grandma” and “grandpa” too)  Nutritional Periodization for Seniors  “Rational Polysupplementation”  BCAAs (esp. Leucine):  “Anti-anorectic” action via hypothalamic serotonergic modulation • Anorexia assoc w/ deranged Trp/5-HT metabolism; Trp/LNAA ratio predict brain 5-HT concentrations [Rossi et al. 1986; Cangiano et al. 1996]  Promoting Protein Synthesis  Inhibiting Proteolytic Pathways [Ventrucci et al. 2004; Paddon-Jones et al. 2004; Poon et al.]
    20. 20. Nutritional Strategies  HMB (and Arg, Lys, Gln) [May et al. 2002; Flakoll et al. 2004]  Protein vs. EAA vs. Prot-NRG  Kinetics (that TIMING thing again)  Feeding Pattern  Leucine “fortification”  Specific EAA profile (over-weighting in certain “high impact” drug-like aminos)  Creatine [Brose et al. 2003]  MVI/ MMI  Strategic Kcal/NRG Restriction vs. a “Metabolic Mimetic”?
    21. 21. Nutritional Strategies Honorable Mention  Anti-Ox supplementation  Potential to improve exercise tolerance, insulin sensitivity, modulate inflammation  KIC  Beta-Alanine  Endocannabinoids  Structured Lipids/ other PPAR- alpha/delta agents  L-Carnitine (PLCAR/ ALCAR)
    22. 22. Exercise Strategies  Targeting FFR motor units  Augment Type IIA (FOG)/ muscle fiber CSA  Role for occasional “Concentric emphasis” sessions for insulin action/sensitvity [Asp S et al. 1996; Kirwan JP et al. 1992]  Resistance Training  The MOST effective long-term intervention for attenuating or preventing sarcopenia [Frontera WR et al. 1988; Charette SL et al. 1991; Lexell J et al. 1995; Vincent KR et al. 2002]  Cadence (3-6s eccentric, 1-2s concentric  progress to more explosive concentric)  High yield compound, multi-joint exercises  Important to account for individual’s training history, limitations, med/surg history
    23. 23. Exercise Strategies  Resistance Training (cont.)  Training parameters for exercise prescription  proper dose response  Volume, Load/ Intensity (70%-95% 1-RM), Frequency, Duration to (Sarcoplasmic vs. Myofibrillar hypertrophy)  Periodize the loading parameters and progressions to stay ahead of the “adaptational curve” (2-5 week intervals)  Modify exercise selection, parameters, program design to “tailor” the exercise Rx long-term • Purposeful, Goal-directed
    24. 24. Exercise Strategies  Resistance Training (cont.)  Strength training using 70-95% of 1RM loads and Eccentric emph   Ultrastructural damage to contractile proteins/ myofibrillar proteolysis [Evans WJ et al. 1991; Frontera WR et al. 1988]  Autocrine/Paracrine IFG, FGF, and PDGF  ↑ prot synth and satellite cell activation [Yamada S et al. 1989; Yan Z et al. 1993]  Decreased Acute Phase Response to RT in elderly (↓CK release, ↓PMN mobilization, IL-1β) and PGs/eicosanoid response  ↓ Adaptation and Remodeling [Goldberg AL et al. 1988; Cannon JG et al. 1994]
    25. 25. Exercise Strategies  Cardiovascular Conditioning/ “Energy Systems Training”  More critical in the Sarcopenic-Obese population  More “permissive” to improve recovery ability and metabolic alterations from HI-RT (i.e. insulin sensitivity, glucose tolerance)  Appropriate Modality for individual  Establish “Base” for ↑ Work Capacity (CO)  Cardiorespiratory testing (likely “higher risk” – ACSM class B, or C)  Wider range of peak HR (50-80%)  Monitoring becomes even more useful  “Steady-state” and “IR-HIIT” protocols after established good base  scaled down appropriately
    26. 26. Exercise Strategies  Other Modalities/ Considerations  FES and “Hybrid”/Dynamic-FES assisted “violates” Henneman’s Size Principle [Mahoney et al. 2005]  Whole body vibration/ “Power plate” options to provide different overload in CKC exercises  Role for VOT/ Acute Focal Ischemia  “Multi-Compound Complexes”  Develop strength and function in multiple planes  Biomechanical/ Functional Anatomy considerations to reduce injury risk and improve training adaptations
    27. 27. Adjunctive Medical Treatment  Anabolic Hormone therapy  AAS (oxandrolone, nandrolone, testosterone esters)  SARMs (Selective Androgen Receptor Modulators; up and coming!)  Peptides (hGH, hGH secretagogues) • Dose/Duration Response  SSRI/SNRIs  “3 birds with one stone”  Mood, Sleep, and Appetite  Examples: Mirtazepine, Trazodone  Megestrol Acetate  Edema and disrupting the HPA axis (A bad thing!)  Insulin Sensitizers (Biguanide class Metformin Vs. TZD- PPAR agonists)  Limit (caution with) NSAID use  affects muscle protein metabolism following eccentric/resistance exercise [Trappe TA et al. 2002]
    28. 28. Adjunctive Medical Treatment  GHRH and IFG-I/IGFBP-3 complex as safer alternatives to GH [Khorram et al. 2000; Vittone et al. 2001;Sullivan DH et al. 1998]  Testosterone replacement generally better tolerated, and more effective in improvement of global functional status outcomes, mood states, and strength (Prostate CA concerns overstated)  Methodologic problems in many previous studies; should adjust for circulating T [Ferrando AA et al. 2002]
    29. 29. General Principles in Sarcopenia Management (Mx)  Nutrition and Exercise Remain the CORNERSTONE of Tx and Px  Resistance exercise confers an amplified anabolic response (MPS) from exogenous AA +/- Insulin  Maximize skel muscle mass during young adult into middle age, to provide reserves as buffer to catabolic stressors  Likely a “threshold” lower limit amount of skeletal muscle, beyond which see multi- organ system dysregulation
    30. 30. General Principles in Sarcopenia Mx  Tailored EAA w/ precise AA profile (e.g. overweighted in Leu, Lys, Phe, Met, etc.)  “Medicine is a science of uncertainty and an art of probablility” -William Osler  Advances in Medicine, Nutrition, and Exercise Science will elucidate previous “uncertainties”…only to open another “abyss of uncertainty”
    31. 31. Salient Points  Sarcopenia  major cause of disability and functional decline  imposes a modifiable economic burden w/ Health Care costs  Multifactorial in origin, thereby requires a multidisciplinary approach  To optimize risk/benefit  regimen focused on nutrition and exercise w/ potential for structured, supervised anabolic Rx  Focus on High-Intensity/Load PRT (relative) to stop or reverse Sarcopenia
    32. 32. Salient Points  Modify Protein and Carb intake to fit the exercise needs/ goals of a particular day  Consider on CV/NRG-sys days: Increased total protein & carb (Pro:1.2g -1.6g/Kg bodyweight); EAA “peri-workout”; ↑CHO/ BCAA/ Leu/ intake throughout  capitalize on increased gluc tolerance/insulin senstivity; limit AA oxidation/catabolism  Consider on Prog-Resistance Training days: (Pro: 1.0g – 1.6g/ Kg/day) with preference to “pulse” midday; ↓CHO/↑Pro/healthy MUFA/PUFAs; high ‘anabolic efficiency’ EAA supplement “flanking” peri-wkt and throughout the recovery period; Leucine “fortification”  facilitate skeletal muscle remodeling; support protein anabolism
    33. 33. Salient PointsSalient Points  Whey over Casein (in supplement); EAA over Balanced AA; Animal over Vegetable  “CHRONO-Nutrition”: ‘Pulse’ feeding pattern w/ 65%-70% daily intake midday (e.g. flanking the exercise session), 10%-15% of highly efficient EAA/protein in am and pm  “Rational Poly-supplementation”:  Leucine and BCAA ‘enriched’ or ‘fortified’ protein feeding/ EAA  EPA/ DHA/ functional lipid supplementation  Creatine w/ different dosing regimens (when and if more data becomes available)  ß-alanine + Creatine + Leucine/BCAA + EAA? (more data needed)
    34. 34. Salient PointsSalient Points  “Rational Poly-supplementation” (cont.):  MVI/MultiMin and comprehensive, low- dose, frequently dosed Antioxidant supp  2nd tier- β-ala, naturally occurring PPAR modulators, Carnitines, etc. (as apporpriate case by case scenario)  Medical management (where appropriate):  Anabolic hormone Rx, Mood/Appetite agents  Molecular targets as they become available  Note: Many of these nutrition/suppl strategies have yet to be studied using larger, RCTs in healthy, elderly population
    35. 35. Anabolic vs. Catabolic Factors in Sarcopenia -Testosterone -IGF/ MGF/ PDGF/ NGF -Insulin Sensitivity -Structured Physical Activity/RT -Adequate Protein/NRG intake/ metabolic response -IL-6 -Ubiquitin-Proteasome/Caspases -TNF-α -tIL-1 -Cent/Periph Anorexic Sig -Atherosclerosis (microcirc) -Decreased α−Motor Neuron fxn -Dec response to key Nutrients/ Hormones CatabolicCatabolic AnabolicAnabolic
    36. 36. Immune System Immune System Endocrine/ Metabolic Endocrine/ Metabolic Musculoskeletal System Musculoskeletal System Neural support Neural support •Vit D/ Ca++/PO4/Mg •Protein •EAA/ BCAA/ HMB/ KIC •Creatine •Functional Lipids •Antioxidants •Β-Alanine •Chondro-protective •7-keto-DHEA •Creatine •Acetyl-L-Car •(other Aminos) •Antioxidants •Funct Lipids •Phosphatidyl Serine •Protein •Gln, Arg, BCAA •Vit D •Antioxidants •Funct Lipids •As Below •ALCar/ PLCar •Insulin Sensitizers (R-ALA, + chiro-inositol, Cinnamon extract, etc.)
    37. 37. Neural Support Immune modulation Muscle Protein synthesis Bioenergetic Substrates Muscle Protein catabolism Myogenic GF & Satellite Cell Activation Systemic/ Local Inflammation Plasma Membrane Support Multiple Pathways for Augmenting the Training Effect and Performance Adaptations from a Complementary Approach
    38. 38. On the HorizonOn the Horizon  Integrating molecular, pharmacologic, exercise, and nutritional disciplines  Biomolecular computing, nano-technology applications  Nutritional/ Exercise/ Pharmaco- Genomics (Biomics tech) • Truly establishing “tailored, precise customization” in Exercise, Nutri/Supp, Molecular targets/Pharma Rx • “Physiatric” Genomics (Applied Exercise, Nutrition, Meds, Rehab based on genomic data for optimizing fxnl capacity, performance, and QOL temp/perm disabled  Seamless Fusion of Medicine, Performance nutrition, Athletic performance, and Wellness (My vision of “FitnessMD- Integrated Medical Fitness model”)
    39. 39. On the HorizonOn the Horizon  FAMuSS study (implications for sports performance, health and sarcopenia)  Exercise, Nutritional and Pharmaco- Genomics/Proteomics  Nascent stages  Not yet changing Mx/Tx (recs benefit the masses despite SNPs and SNP frequency)  May alter ‘aggressiveness’ of Mx/Tx (management/ treatment)  Next Frontier brings “precise customization” w/ molecular targets, nutrition, and exercise
    40. 40. To learn more or ask a question, click here to contact Dr. Lopez at www.drhectorlopez.com Thanks for viewing!Thanks for viewing!